New and irreversible modifications of genomic structure are induced in Plasmodium when the malaria parasite is subjected to stress. These modifications give rise to altered patterns of gene expression which modulate the parasite phenotype. Conditions known to induce genomic changes include drug pressure, growth environments imposed by in vitro culture, cross-fertilization between different parasite genomes, and antibody pressure. We now have the capability to enumerate, size and map chromosomes of Plasmodium. We are working to characterize the details of chromosome organization and genomic alterations induced by stress.